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Driver mutations lung cancer

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https://www.readbyqxmd.com/read/29036791/globo-h-expression-is-associated-with-driver-mutations-and-pd-l1-expressions-in-stage-i-non-small-cell-lung-cancer
#1
Ching-Yao Yang, Mong-Wei Lin, Yih-Leong Chang, Chen-Tu Wu
BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1)...
September 29, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29034207/targeting-novel-but-less-common-driver-mutations-and-chromosomal-translocations-in-advanced-non-small-cell-lung-cancer
#2
REVIEW
Alia Daoud, Quincy S Chu
Discovery of the epidermal growth factor receptor gene mutation and the anaplastic lymphoma kinase chromosomal translocation in non-small cell lung cancer has prompted efforts around the world to identify many less common targetable oncogenic drivers. Such concerted efforts have been variably successful in both non-squamous and squamous cell carcinomas of the lung. Some of the targeted therapies for these oncogenic drivers have received regulatory approval for clinical use, while others have modest clinical benefit...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29029508/efficiency-of-low-dosage-apatinib-in-post-first-line-treatment-of-advanced-lung-adenocarcinoma
#3
Da-Xiong Zeng, Chang-Guo Wang, Wei Lei, Jian-An Huang, Jun-Hong Jiang
Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29018192/simultaneous-evolutionary-expansion-and-constraint-of-genomic-heterogeneity-in-multifocal-lung-cancer
#4
Pengfei Ma, Yujie Fu, Mei-Chun Cai, Ying Yan, Ying Jing, Shengzhe Zhang, Minjiang Chen, Jie Wu, Ying Shen, Liang Zhu, Hong-Zhuan Chen, Wei-Qiang Gao, Mengzhao Wang, Zhenyu Gu, Trever G Bivona, Xiaojing Zhao, Guanglei Zhuang
Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28993799/genetic-characterization-of-brain-metastases-in-the-era-of-targeted-therapy
#5
REVIEW
Catherine H Han, Priscilla K Brastianos
In the current era of molecularly targeted therapies and precision medicine, choice of cancer treatment has been increasingly tailored according to the molecular or genomic characterization of the cancer the individual has. Previously, the clinical observation of inadequate control of brain metastases was widely attributed to a lack of central nervous system (CNS) penetration of the anticancer drugs. However, more recent data have suggested that there are genetic explanations for such observations. Genomic analyses of brain metastases and matching primary tumor and other extracranial metastases have revealed that brain metastases can harbor potentially actionable driver mutations that are unique to them...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28991240/polypharmacology-based-ceritinib-repurposing-using-integrated-functional-proteomics
#6
Brent M Kuenzi, Lily L Remsing Rix, Paul A Stewart, Bin Fang, Fumi Kinose, Annamarie T Bryant, Theresa A Boyle, John M Koomen, Eric B Haura, Uwe Rix
Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strategy, here we describe the anaplastic lymphoma kinase (ALK) inhibitor ceritinib as having activity across several ALK-negative lung cancer cell lines and identify new targets and network-wide signaling effects...
October 9, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28987609/structure-based-design-and-synthesis-of-2-4-diaminopyrimidines-as-egfr-l858r-t790m-selective-inhibitors-for-nsclc
#7
Lingfeng Chen, Weitao Fu, Chen Feng, Rong Qu, Linjiang Tong, Lulu Zheng, Bo Fang, Yinda Qiu, Jie Hu, Yuepiao Cai, Jianpeng Feng, Hua Xie, Jian Ding, Zhiguo Liu, Guang Liang
Mutated epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). The EGFR(T790M) secondary mutation has become a leading cause of clinically-acquired resistance to gefitinib and erlotinib. Herein, we present a structure-based design approach to increase the potency and selectivity of the previously reported reversible EGFR inhibitor 7, at the kinase and cellular levels. Three-step structure-activity relationship exploration led to promising compounds 19e and 19h with unique chemical structure and binding mode from the other third-generation tyrosine kinase inhibitors...
September 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28979142/the-non-small-cell-lung-cancer-egfr-extracellular-domain-mutation-m277e-is-oncogenic-and-drug-sensitive
#8
Su Yu, Yang Zhang, Yunjian Pan, Chao Cheng, Yihua Sun, Haiquan Chen
PURPOSE: To identify novel oncogenic mutations in non-small cell lung cancer patient specimens that lack mutations in known targetable genes ("pan-negative" patients). METHODS: Comprehensive mutational analyses were performed on 1,356 lung adenocarcinoma specimens. In this cohort of patients, common lung cancer oncogenic driver mutations were detected in the epidermal growth factor receptor (EGFR) kinase domain, the human epidermal growth factor receptor 2 kinase domain, as well as the KRAS, BRAF, ALK, ROS1 and RET genes...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28978153/concurrent-somatic-mutations-in-driver-genes-were-significantly-correlated-with-lymph-node-metastasis-and-pathological-types-in-solid-tumors
#9
Yanan Cheng, Shaojing Wang, Lei Han, Pengpeng Liu, Hui Li, Xiubao Ren, Jinpu Yu, Xishan Hao
To demonstrate the mutational profiles in solid tumors, we profiled 165 solid tumor samples, including 9 cancer types and 4 sample types, by using amplicon-based next-generation sequencing panel covering 48 highly mutated tumorigenesis-related genes that were deep sequenced at an average coverage of 2000×. Both tumor and sample types had significant effect on tumor genetic mutational profiles. Concurrent driver mutations were frequently detected in solid tumor, concentrating on both modes of action driver genes (activating or loss of function)...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28971587/concurrent-ros1-gene-rearrangement-and-kras-mutation-in-lung-adenocarcinoma-a-case-report-and-literature-review
#10
You-Cai Zhu, Xue-Ping Lin, Xiao-Feng Li, Li-Xin Wu, Hua-Fei Chen, Wen-Xian Wang, Chun-Wei Xu, Jian-Fa Shen, Jian-Guo Wei, Kai-Qi Du
Lung adenocarcinomas with gene rearrangement in the receptor tyrosine kinase ROS1 have emerged as a rare molecular subtype. Although these lung adenocarcinomas respond to ROS1tyrosine kinase inhibitors, many patients ultimately acquire resistance. ROS1gene rearrangement is generally mutually exclusive with other driver genomic alterations, such as those in EGFR, KRAS, or ALK, thus multiple genomic alterations are extremely rare. Herein, we report a case of a 42-year-old man diagnosed with lung adenocarcinoma positive for a SDC4-ROS1 fusion, who was treated with crizotinib followed by three cycles of chemotherapy...
October 3, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28951454/genomic-landscape-of-atypical-adenomatous-hyperplasia-reveals-divergent-modes-to-lung-adenocarcinoma
#11
Smruthy Sivakumar, F Anthony San Lucas, Tina L McDowell, Wenhua Lang, Li Xu, Junya Fujimoto, Jianjun Zhang, P Andrew Futreal, Junya Fukuoka, Yasushi Yatabe, Steven M Dubinett, Avrum E Spira, Jerry Fowler, Ernest T Hawk, Ignacio I Wistuba, Paul Scheet, Humam Kadara
There is a dearth of knowledge about the pathogenesis of premalignant lung lesions, especially for atypical adenomatous hyperplasia (AAH), the only known precursor for the major lung cancer subtype adenocarcinoma (LUAD). In this study, we performed deep DNA and RNA sequencing analyses of a set of AAH, LUAD and normal tissues. Somatic BRAF variants were found in 5/22 (23%) of AAH patients, 4/5 of whom had matched LUAD with driver EGFR mutations. KRAS mutations were present in all ever-smoker cases in the cohort (18%) exclusive of the cases with BRAF mutations...
September 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28949084/comprehensive-genomic-profiling-of-lung-cancer-using-a-validated-panel-to-explore-therapeutic-targets-in-east-asian-patients
#12
Liping Liu, Jilong Liu, Di Shao, Qiuhua Deng, Hailing Tang, Zu Liu, Xuewei Chen, Fengming Guo, Yongping Lin, Mao Mao, Karsten Kristiansen, Mingzhi Ye, Jianxing He
People of East Asian ethnicity show unique clinical characteristics, tumour histology, and different prevalence of oncogenic mutations. However, only limited studies have explored the landscape of genomic alterations in lung adenocarcinoma derived from Asian patients thus far. In this single centre study, with an aim to elucidate the mutational profile of lung cancer in people of Chinese ethnicity and to use the obtained information to guide decision making for treatment, we employed a well-validated assay to perform comprehensive genomic characterization of tumour specimens from 306 Chinese lung cancer patients...
September 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28947568/discrimination-of-germline-egfr-t790m-mutations-in-plasma-cell-free-dna-allows-study-of-prevalence-across-31-414-cancer-patients
#13
Yuebi Hu, Ryan S Alden, Justin I Odegaard, Stephen R Fairclough, Ruthia Chen, Jennifer Heng, Nora Feeney, Rebecca Nagy, Jayshree Shah, Bryan Ulrich, Martin Gutierrez, Richard B Lanman, Judy E Garber, Cloud P Paweletz, Geoffrey R Oxnard
PURPOSE: Plasma cell-free DNA (cfDNA) analysis is increasingly used clinically for cancer genotyping, but may lead to incidental identification of germline risk alleles. We studied EGFR T790M mutations in non-small cell lung cancer (NSCLC) toward the aim of discriminating germline and cancer-derived variants within cfDNA. EXPERIMENTAL DESIGN: Patients with EGFR-mutant NSCLC, some with known germline EGFR T790M, underwent plasma genotyping. Separately, deidentified genomic data and buffy coat specimens from a clinical plasma next-generation sequencing (NGS) laboratory were reviewed and tested...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28935493/update-on-egfr-mutational-testing-and-the-potential-of-noninvasive-liquid-biopsy-in-non-small-cell-lung-cancer
#14
REVIEW
Edward Kim, Rebecca Feldman, Ignacio I Wistuba
Mutations in the epidermal growth factor receptor (EGFR) are important drivers of non-small-cell lung cancer (NSCLC) and have led to the emergence of EGFR-targeted therapies as critical treatment options for NSCLC. Although these agents have shown clinical activity in NSCLC patients, acquired resistance to EGFR-targeted agents is inevitable. Therefore, the ability to conveniently biopsy patient tumors is of increasing importance as new mechanisms of resistance and agents to target these resistance mutations are identified...
August 12, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28935015/-egfr-and-kras-gene-mutations-in-754-patients-with-resectable-stage-i-iiia-non-small-cell-lung-cancer-and-its-clinical-significance
#15
Jing Zhao, Jie Gao, Liping Guo, Xiaoxu Hu, Qi Liu, Jinyin Zhao, Licheng Liu, Jun Jiang, Mengzhao Wang, Zhiyong Liang, Yan Xu, Minjiang Chen, Li Zhang, Longyun Li, Wei Zhong
BACKGROUND: Epidermal growth factor receptor (EGFR) and KRAS gene are important driver genes of non-small cell lung cancer (NSCLC). The studies are mainly focused on detection of EGFR gene for advanced NSCLC, and the mutation feature of EGFR and KRAS gene in early NSCLC tissue is unknown. This study aims to investigate the mutations of EGFR and KRAS gene in NSCLC, and the relationship between the genotype and clinicopathologic features. METHODS: The hotspot mutations in EGFR and KRAS gene in 754 tissue samples of stage I-IIIa NSCLC from Department of Pathology, Peking Union Medical College Hospital were detected by modified amplification refractory mutation system (ARMS) real-time PCR kit, and analyzed their correlation with clinical variables...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28932565/unique-distribution-of-programmed-death-ligand-1-pd-l1-expression-in-east-asian-non-small-cell-lung-cancer
#16
Yunjian Pan, Difan Zheng, Yuan Li, Xu Cai, Zongli Zheng, Yan Jin, Haichuan Hu, Chao Cheng, Lei Shen, Jian Wang, Hongbin Ji, Yihua Sun, Xiaoyan Zhou, Haiquan Chen
BACKGROUND: To determine the proportion and clinical features of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer (NSCLC). METHODS: PD-L1 expression was assessed by immunohistochemistry (IHC) and tumor proportion score (TPS) with the use of PD-L1 IHC 22C3 antibody (Dako North America) in 108 surgically resected lung squamous cell carcinomas (SCC) and 221 lung adenocarcinomas (LUADs), and was correlated with clinical variables, histologic subtypes, and common driver mutations...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#17
Jin Li, Yaoqi Chen, Xiaoshun Shi, Xiaobing Le, Fenglan Feng, Jingyi Chen, Chengzhi Zhou, Yusong Chen, Shuai Wen, Haikang Zeng, Allen M Chen, Yu Zhang
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28919011/dabrafenib-plus-trametinib-in-patients-with-previously-untreated-braf-v600e-mutant-metastatic-non-small-cell-lung-cancer-an-open-label-phase-2-trial
#18
MULTICENTER STUDY
David Planchard, Egbert F Smit, Harry J M Groen, Julien Mazieres, Benjamin Besse, Åslaug Helland, Vanessa Giannone, Anthony M D'Amelio, Pingkuan Zhang, Bijoyesh Mookerjee, Bruce E Johnson
BACKGROUND: BRAF(V600E) mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAF(V600E)-mutant metastatic NSCLC. METHODS: In this phase 2, sequentially enrolled, multicohort, multicentre, non-randomised, open-label study, adults (≥18 years of age) with previously untreated metastatic BRAF(V600E)-mutant NSCLC were enrolled into cohort C from 19 centres in eight countries within North America, Europe, and Asia...
October 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28915716/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#19
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911955/brief-report-somatic-mutations-and-ancestry-markers-in-hispanic-lung-cancer-patients
#20
Nicholas T Gimbrone, Bhaswati Sarcar, Edna R Gordian, Jason I Rivera, Christian Lopez, Sean J Yoder, Jamie K Teer, Eric A Welsh, Alberto A Chiaporri, Matthew B Schabath, Gary W Reuther, Julie Dutil, Miosotis Garcia, Ronald Ventosilla-Villanueva, Luis Vera-Valdivia, Alejandro Yabar-Berrocal, Rodrigo Motta-Guerrero, Pedro G Santiago-Cardona, Teresita Muñoz-Antonia, W Douglas Cress
INTRODUCTION: To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients. METHODS: This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, STK11, and TP53) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and were correlated with ancestry, sex, smoking status, and tumor histology...
September 11, 2017: Journal of Thoracic Oncology
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